Growth, puberty, and endocrine functions in patients with sporadic or familial neurofibromatosis type 1: a longitudinal study.
ABSTRACT This study prospectively evaluates parameters of growth, puberty, and attained adult height in children with sporadic or familial occurrence of neurofibromatosis type 1 (NF-1), followed up longitudinally, to define the most important factors affecting these parameters.
The study was made up of 89 patients (55 boys, 34 girls) with sporadic (n = 45) or familial NF-1 (13 affected fathers and 31 affected mothers). The average age at referral was 8.9 years (range 8.5-15 years), and the average follow-up period was 8.5 years (6-15 years). A total of 28 patients attained adult height at the time of the report. Anthropometric measurements and bone age determinations were performed at 6- to 12-month intervals. As indicated, central nervous system (CNS) imaging was performed on 60 patients. Serum levels of thyroid stimulating hormone, free T4, lutheinizing hormone, follicle stimulating hormone, testosterone or estradiol, cortisol, and prolactin were measured in all patients periodically, and the pituitary growth hormone reserve was assessed in 32 short patients.
CNS pathology was found in 23 of the 89 patients. A total of 6 patients required neurosurgery, and 2 patients had cranial irradiation. Of these patients, 3 were receiving recombinant growth hormone and thyroxin replacement therapy and 5 patients with precocious puberty were treated with a gonadotropin-releasing hormone analog. All other patients had normal endocrine tests. Precocious puberty was recorded in 5 patients and was more common among the familial cases. The 5 patients with precocious puberty also had CNS pathology. Short stature (<10th percentile) was observed in 25.5% of the patients during the prepubertal period with a significant gradual reduction of their relative height for age (standard scores) during puberty. Short adult height was noted in 12 (43%) of 28 patients, and only 50% of the 28 patients attained an adult height that was appropriate for their respective target height. Short stature was more common among patients with familial NF-1, particularly if the father was affected, and among those patients with CNS pathology. Parental short stature was observed in 39% of the mothers and in 33% of the fathers (59% and 54% among the affected parents, respectively). Tall stature (>90th percentile) was observed in 4 of 89 patients (4.5%), who all had CNS tumors. A highly significant correlation was found among all adult height-predicting parameters (r =.79), and attained adult height was best correlated with the target height (r =.7; n = 28).
Short adult height is an important characteristic of NF-1 and deserves to be emphasized in the evaluation and follow-up of these patients during childhood. Short adult height is strongly linked with familial background of NF-1, in particular if the affected parent is the father, and is affected adversely by the relatively poor pubertal growth. Despite normal pituitary gland and thyroid function tests in most children and adolescents with NF-1, increased incidence of precocious puberty was observed. As the clinical expression in the second generation is more pronounced, the underlying mechanism seems to be mediated by genetic factors that are yet undefined.
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ABSTRACT: GH and IGF-I have been shown to affect tumor growth in vitro and in some animal models. This report summarizes the available evidence on whether GH therapy in childhood is associated with an increased risk of neoplasia during or after treatment is completed. PubMed search conducted through February 2014retrieved original articles written in English addressing GH therapy and neoplasia risk. Subsequent searches were done to include additional relevant publications. In children without prior cancer or known risk factors for developing cancer, the clinical evidence does notaffirm an association between GH therapy during childhood and neoplasia. GH therapy has not been reported to increase risk for neoplasia in this population, although most of these data are derived from post-marketing surveillance studies lacking rigorous controls. In patients who are at higher risk for developing cancer, current evidence is insufficient to conclude whether or not GH further increases cancer risk. GH treatment of pediatric cancer survivors does not appear to increase the risk of recurrence, but may increase their risk for subsequent primary neoplasms. In children without known risk factors for malignancy, GH therapy can be safely administered without concerns about an increased risk for neoplasia. GH use in children with medical diagnoses predisposing them to development of malignancies should be critically analyzed on an individual basis, and if chosen, appropriate surveillance for malignancies should be undertaken. GH can be used to treat GH deficient childhood cancer survivors who are in remission with the understanding that GH therapy may increase their risk for second neoplasms.The Journal of Clinical Endocrinology and Metabolism 04/2015; DOI:10.1210/jc.2015-1002 · 6.31 Impact Factor
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ABSTRACT: We report the case of a 31 year-old male from Cajamarca, Peru, with cognitive problems since childhood, who at 12 year-old developed increased volume and deformation of his right lower limb and to a lesser extent of his left, associated to massive skin folding, growth of subcutaneous nodules, elephantine look due to nerve cords formation in thigh and leg, pain and functional walking limitation. Concomitantly generalized skin café au lait spots, subcutaneous nodules, and Lisch nodules in both irides. Magnetic resonance and contrast TAC revealed abundant uniform plexiform nodules in abdomino-pelvic cavity forming masses and cords that continued throughout his thigh as lumps and cords. In addition, the patient presented bone dysplasia (thinning of femur and tibia cortex, pseudoarthrosis, new left cotyle formation). Contrast magnetic resonance showed triventricular normotensive hydrocephalus.09/2009; 70(3):205-210.
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ABSTRACT: Die Neurofibromatose Typ 1 (NF1) ist eine häufige, autosomal-dominant erbliche Phakomatose. Die Diagnostik, basierend auf den NIH- (,,National Institutes of Health-“) Kriterien, führt oftmals im Kindesalter zu einer verzögerten Krankheitserkennung.Deutschlandweit wurden 102 NF1-Patienten (im Mittel 10,8 Jahre alt) untersucht. Neben den NIH-Diagnosekriterien wurden die erste Dentition, Körpergewicht, Körpergröße und Kopfumfang von der U1 bis U9 dokumentiert und einem Kontrollkollektiv von 51 gesunden Geschwistern sowie einer Gruppe gesunder, nicht verwandter Kinder gegenübergestellt.Der Anteil der Frühzahner war mit 31% unter den NF1-Patienten im Vergleich zu gesunden Geschwistern erhöht (8,9%). Körpergröße und Körpergewicht der NF1-Patienten unterschieden sich in den ersten 5 Lebensjahren nicht signifikant von gleichaltrigen gesunden Kindern. Jedoch hatten NF1-Patienten ab dem vollendeten 1. Jahr einen signifikant größeren Kopfumfang.Der hohe Anteil an Frühzahnern und der größere Kopfumfang ab dem vollendeten 1. Lebensjahr können den Verdacht auf das Vorliegen einer NF1 verstärken. Die Diagnostik in den ersten 5 Lebensjahren sollte deshalb vor allem bei Kindern auf Verdacht einer Neumutation auch Nebensymptome wie Makrozephalus und eine verfrühte Dentition umfassen.Monatsschrift Kinderheilkunde 01/2008; 156(9). · 0.28 Impact Factor